This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The Study of Heart and Renal Protection (SHARP) will assess the effects of a combination of simvastatin and the cholesterol-absorption inhibitor ezetimibe among approx. 9,000 patients with chronic kidney disease (CKD) -around 6,000 of who will be pre-dialysis and 3,000 on dialysis at randomization. First, observational studies among dialysis patients have reported a negative association between blood total cholesterol and mortality. Secondly, only about one quarter of cardiac mortality in such patients appears to be definitely attributable to acute myocardial infarction, and potentially avoidable with cholesterol-lowering, while the other common causes (e.g. cardiac arrest, arrhythmia, and heart failure) may not be as dependent on cholesterol levels. Finally, the long-term safety of cholesterol reduction among patients with CKD remains unclear. The primary aim of SHARP is to assess the effects of lowering LDL cholesterol with combined simvastatin 20 mg and ezetimide 10 mg versus placebo on the time to a first major vascular event (defined as non-fatal myocardial infarction or cardiac death, non-fatal or fatal stroke, or revascularisation). Secondary aims of the study include an assessment of the effects of ezetimibe/simvastatin on: progression to end-stage renal disease (among pre-dialysis patients);various causes of death;major cardiac events (defined as non-fatal MI or cardiac death);stroke and hospitalization for angina. Fifty subjects will be entered into this study at Meharry, including pre-dialysis and dialysis patients.